VON WILLEBRAND DISEASE:

LABORATORY EVALUATION
BloodCenter of Wisconsin Hemostasis Reference Laboratory specializes in
comprehensive testing for von Willebrand disease.

BACKGROUND:
von Willebrand disease (VWD) is a common bleeding disorder characterized by
either quantitative or qualitative defects of von Willebrand factor (VWF).
Screening tests for VWD include Factor VIII activity, VWF antigen, and VWF
ristocetin cofactor activity. Discrepancies between VWF antigen and activity
levels suggest a variant of VWD. Correct diagnosis of variant VWD is essential
to providing effective treatment.
von Willebrand Types
Type: 1 2A 2B 2M 2N 3 Platelet-type
Test
VWF Antigen ↓ ↓ ↓/N ↓/N ↓/N <1 ↓/N

VWF Ristocetin ↓ D ↓↓ D ↓/N D ↓↓ ↓/N < 10 D↓/N

Cofactor Activity

VWF Collagen ↓ D↓↓ D ↓/N ↓/N ↓/N <1 D↓/N

Binding Activity

VWF Multimers N Abn Abn N N None Abn

VWF-FVIII (2N) N N N N Abn N/A N

Binding Assay

VWF-Platelet N N Abn N N N/A N

(2B) Binding
Assay

Low Dose RIPA N N Abn N N N Abn

FVIII Activity ↓/N ↓/ N ↓/N ↓/N D ↓↓ ↓↓ ↓/N

N Normal
Abn Abnormal
N/A not applicable
↓ reduced
D↓ discrepancy between reduction in activity as compared to VWF antigen
RIPA ristocetin induced platelet aggregation

CONTACT US:
Phone 414-937-6250 Fax 414-937-6202
Mailing Address: PO Box 2178; Milwaukee, WI 53201-2178
Delivery Address: 638 N. 18 St.; Milwaukee, WI 53233-2121
Email: labinfo@bcw.edu Website: www.bcw.edu

See reverse for test list.

PO Box 2178, Milwaukee, WI 53201-2178 • Sample Deliveries: 638 N. 18 St. Milwaukee, WI 53233 • 414-937-6250
www.bcw.edu
TESTS AVAILABLE:

von Willebrand Profile

Includes VWF Antigen, VWF Ristocetin Cofactor Activity, VWF Multimers, Factor
VIII Activity, and ABO blood group by reverse typing. This set of tests provides
sufficient information to support a clinical diagnosis of VWD. Additional testing is
required for classification of variant VWD.

VWF Multimer Analysis

VWF is synthesized as a multimeric Multimer Analysis
protein. That is, VWF exists as an array

Platelet Type
of large molecules comprising different
numbers of its basic subunit. Higher

Type 2M

Type 2N
Type 2A

Type 2B
Normal

Type 1

Type 3
molecular weight multimers are more
effective in initiating hemostasis at sites
of vascular injury. Loss of high molecular
weight multimers is a hallmark of type
2A, 2B and platelet-type VWD.

VWF Collagen Binding (VWF:CB)

In vivo, collagen binding by VWF facilitates platelet adhesion at sites of blood
vessel injury. The collagen binding assay tests this capacity, and discrepancy
between VWF:CB and VWF antigen levels is a sensitive screen for von
Willebrand disease subtypes in which large molecular weight multimers are
missing (type 2A, 2B and platelet-type VWD).

VWD Type 2N Binding (VWF-FVIII Binding)

In Type 2N VWD, the binding of factor VIII to VWF is reduced. In patients with
reduced levels of factor VIII, the Type 2N Binding Assay differentiates type 2N
VWD from mild hemophilia A or hemophilia A carrier state.

VWD Type 2B Binding (VWF-Platelet Binding)

Type 2B VWD is caused by an increase in VWF binding to platelets, and a
resulting loss of larger VWF multimers. The Type 2B Binding Assay
differentiates type 2B VWD from platelet-type VWD.

Sequence Analysis
Some rare cases of variant VWD may require DNA sequencing to confirm the
diagnosis. Type 2N Sequence Analysis will identify mutations in the VWF exons
which encode for factor VIII binding domains. VWF Exon 28 Sequence Analysis
will identify mutations associated with type 2A, 2B and 2M VWD, and VWD
Platelet-Type Sequence Analysis identifies mutations in platelet glycoprotein
Ibalpha associated with platelet type VWD.

Other Tests for VWD

Ristocetin Induced Platelet Aggregation VWF Antigen
VWF Inhibitor VWF Ristocetin Cofactor Activity
VWF Propeptide Antigen FWIII Activity
January 2009
PO Box 2178, Milwaukee, WI 53201-2178 • Sample Deliveries: 638 N. 18 St. Milwaukee, WI 53233 • 414-937-6250
www.bcw.edu